Prevention of corticosteroid-induced bone loss with alendronate.
The putitive bone-sparing effect of alendronate was tested in two animal models of osteopenia: estrogen-deficient female rats and glucocorticoid-treated male rats. In the first study, 18 female Sprague-Dawley rats, 4 months of age, were ovariectomized (OVX), and an additional 6 rats were sham-operated. The OVX rats were treated with either vehicle, 17beta-estradiol (E2) (100 microg/rat/week, s.c.), or alendronate (1 mg/kg/day, on alternate days, orally). In the second study, 24 8-month-old male Wistar rats were treated with either vehicle, methyl prednisolone (7 mg/kg once a week, s.c.), prednisolone plus testosterone (16 mg/kg once every 3 weeks, i.m.), or prednisolone plus alendronate (20 microg/kg twice a week, s.c.). Prior to treatment and at the end of the 6-week treatment period, bone mineral density (BMD) of the lumbar spine was measured by dual energy x-ray absorptiometry, and mean femur weights were calculated. The OVX rats had subnormal BMD (-3.91 +/- 1.0% vs control +5.19 +/- 3.92%, P < 0.05) and femur weights (720 +/- 6 mg vs %; 746 +/- 11 mg, P < 0.05). OVX-induced bone loss was completely abolished by the administration of E2 (7.01 +/- 2.32%, P < 0.005; 748 +/- 6 mg, P < 0.01), or alendronate (24.2 +/- 2.73%, P < 0.0001; 779 +/- 11 mg, P < 0.001). In the second study in older male rats, glucocorticoids significantly decreased BMD (-9.70 +/- 3.44% vs -1.10 +/- 1.75%, P < 0.05), and femur weight (1070 +/- 14 mg vs 1180 +/- 24 mg, P < 0.01). Concomitant administration of testosterone (BMD 4.23 +/- 1.84%, P < 0.005; femur weight 1260 +/- 56 mg, P < 0.02), or alendronate (BMD 8.18 +/- 1.36%, P < 0.001; femur weight 1360 +/- 50 mg) with prednisolone, abolished the corticosteroid-induced bone loss. Bone histomorphometry showed a 34% loss of trabecular bone volume in glucocorticoid-treated rats (P < 0.05), which was prevented with both testosterone and alendronate therapies. However, at the doses used in both models, alendronate was more efficacious than either E2 or testosterone in increasing BMD and femur weight. In summary, this study demonstrated that alendronate therapy is highly effective in counteracting the osteopenia of OVX and glucocorticoid therapy.
Wimalawansa
S J
SJ
Department of Internal Medicine, The University of Texas Medical Branch at Galveston, 77555-1065, USA. swimalaw@utmb.edu
Simmons
D J
DJ
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology; D005260:Female; D005269:Femur; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000517:prevention & control; D010052:Ovariectomy; D011239:Prednisolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D004967:Estrogens; D015675:Osteocalcin; D013739:Testosterone; D004958:Estradiol; D011239:Prednisolone; D019386:Alendronate; D008775:Methylprednisolone